tbuckley/cabot-search huggingface dataset:
Polygenic profiles define aspects of clinical heterogeneity in attention deficit hyperactivity disorder
Authors: Sonja LaBianca, Isabell Brikell, Dorte Helenius, Robert Loughnan, Joel Mefford, Clare E. Palmer, Rebecca Walker, Jesper R. Gådin, Morten Krebs, Vivek Appadurai, Morteza Vaez, Esben Agerbo, Marianne Giørtz Pedersen, Anders D. Børglum, David M. Hougaard, Ole Mors, Merete Nordentoft, Preben Bo Mortensen, Kenneth S. Kendler, Terry L. Jernigan, Daniel H. Geschwind, Andrés Ingason, Andrew W. Dahl, Noah Zaitlen, Søren Dalsgaard, Thomas M. Werge, Andrew J. Schork
Journal: Nature Genetics (2023)
Dynamic regulatory elements in single-cell multimodal data implicate key immune cell states enriched for autoimmune disease heritability
Authors: Anika Gupta, Kathryn Weinand, Aparna Nathan, Saori Sakaue, Martin Jinye Zhang, Laura Donlin, Kevin Wei, Alkes L. Price, Tiffany Amariuta, Soumya Raychaudhuri
Journal: Nature Genetics (2023)
Mapping the dynamic genetic regulatory architecture of HLA genes at single-cell resolution
Authors: Joyce B. Kang, Amber Z. Shen, Saisriram Gurajala, Aparna Nathan, Laurie Rumker, Vitor R. C. Aguiar, Cristian Valencia, Kaitlyn A. Lagattuta, Fan Zhang, Anna Helena Jonsson, Seyhan Yazar, Jose Alquicira-Hernandez, Hamed Khalili, Ashwin N. Ananthakrishnan, Karthik Jagadeesh, Kushal Dey, Jennifer Albrecht, William Apruzzese, Nirmal Banda, Jennifer L. Barnas, Joan M. Bathon, Ami Ben-Artzi, Brendan F. Boyce, David L. Boyle, S. Louis Bridges, Vivian P. Bykerk, Debbie Campbell, Hayley L. Carr, Arnold Ceponis, Adam Chicoine, Andrew Cordle, Michelle Curtis, Kevin D. Deane, Edward DiCarlo, Patrick Dunn, Andrew Filer, Gary S. Firestein, Lindsy Forbess, Laura Geraldino-Pardilla, Susan M. Goodman, Ellen M. Gravallese, Peter K. Gregersen, Joel M. Guthridge, V. Michael Holers, Diane Horowitz, Laura B. Hughes, Kazuyoshi Ishigaki, Lionel B. Ivashkiv, Judith A. James, Gregory Keras, Ilya Korsunsky, Amit Lakhanpal, James A. Lederer, Myles Lewis, Zhihan J. Li, Yuhong Li, Katherine P. Liao, Arthur M. Mandelin, Ian Mantel, Kathryne E. Marks, Mark Maybury, Andrew McDavid, Mandy J. McGeachy, Joseph Mears, Nida Meednu, Nghia Millard, Larry W. Moreland, Saba Nayar, Alessandra Nerviani, Dana E. Orange, Harris Perlman, Costantino Pitzalis, Javier Rangel-Moreno, Karim Raza, Yakir Reshef, Christopher Ritchlin, Felice Rivellese, William H. Robinson, Ilfita Sahbudin, Anvita Singaraju, Jennifer A. Seifert, Kamil Slowikowski, Melanie H. Smith, Darren Tabechian, Dagmar Scheel-Toellner, Paul J. Utz, Gerald F. M. Watts, Kevin Wei, Kathryn Weinand, Dana Weisenfeld, Michael H. Weisman, Aaron Wyse, Qian Xiao, Zhu Zhu, Mark J. Daly, Ramnik J. Xavier, Laura T. Donlin, Jennifer H. Anolik, Joseph E. Powell, Deepak A. Rao, Michael B. Brenner, Maria Gutierrez-Arcelus, Yang Luo, Saori Sakaue, Soumya Raychaudhuri
Journal: Nature Genetics (2023)
Sustained hyperglycemia specifically targets translation of mRNAs for insulin secretion
Authors: Abigael Cheruiyot, Jennifer Hollister-Lock, Brooke Sullivan, Hui Pan, Jonathan M. Dreyfuss, Susan Bonner-Weir, Jean E. Schaffer
Journal: Journal of Clinical Investigation (2023)

Pancreatic β cells are specialized for coupling glucose metabolism to insulin peptide production and secretion. Acute glucose exposure robustly and coordinately increases translation of proinsulin and proteins required for secretion of mature insulin peptide. By contrast, chronically elevated glucose levels that occur during diabetes impair β cell insulin secretion and have been shown experimentally to suppress insulin translation. Whether translation of other genes critical for insulin secretion is similarly downregulated by chronic high glucose is unknown. Here, we used high-throughput ribosome profiling and nascent proteomics in MIN6 insulinoma cells to elucidate the genome-wide impact of sustained high glucose on β cell mRNA translation. Before induction of ER stress or suppression of global translation, sustained high glucose suppressed glucose-stimulated insulin secretion and downregulated translation of not only insulin, but also mRNAs related to insulin secretory granule formation, exocytosis, and metabolism-coupled insulin secretion. Translation of these mRNAs was also downregulated in primary rat and human islets following ex vivo incubation with sustained high glucose and in an in vivo model of chronic mild hyperglycemia. Furthermore, translational downregulation decreased cellular abundance of these proteins. Our study uncovered a translational regulatory circuit during β cell glucose toxicity that impairs expression of proteins with critical roles in β cell function.
Biofilm-derived oxylipin 10-HOME–mediated immune response in women with breast implants
Authors: Imran Khan, Robert E. Minto, Christine Kelley-Patteson, Kanhaiya Singh, Lava Timsina, Lily J. Suh, Ethan Rinne, Bruce W. Van Natta, Colby R. Neumann, Ganesh Mohan, Mary Lester, R. Jason VonDerHaar, Rana German, Natascia Marino, Aladdin H. Hassanein, Gayle M. Gordillo, Mark H. Kaplan, Chandan K. Sen, Marshall E. Kadin, Mithun Sinha
Journal: Journal of Clinical Investigation (2023)

The study investigates a mechanistic link if bacterial biofilm mediated host-pathogen interaction leads to immunological complications associated with breast implant illness (BII). Over 10 million women worldwide have breast implants. In recent years, women have described a constellation of immunological symptoms believed to be related to their breast implants. The study included 178 subjects divided in three cohorts. Eighty-six patients reported symptoms consistent with BII. Control group I (non-BII, N=55) included patients with breast implants without BII symptoms but went through explantation of the breast implant. Control group II (normal tissue, N=37) was comprised of women without an implant, whose breast tissue was removed as an unrelated clinically indicated surgical procedures. We report that periprosthetic breast tissue of BII had increased abundance of biofilm and biofilm-derived oxylipin, 10-HOME. S. epidermidis biofilm was observed to be higher in the BII group (73.33%) compared to non-BII group (16.67%, p=0.018) and the normal group (10%, p=0.036). The oxylipin was found to be immunogenic capable of polarizing naïve CD4+ T cells with a resulting Th1 subtype in vitro and in vivo. Consistently, an abundance of CD4+Th1 subtype was observed in the periprosthetic breast tissue and blood of BII subjects. Mice injected with 10-HOME also had increased Th1 subtype in blood akin to BII patients and demonstrated fatigue-like symptoms. The identification of an oxylipin-mediated mechanism of immune activation induced by local bacterial biofilm associated with BII provides insight into the possible pathogenesis of implant-associated immune symptoms of BII.
High-dimensional multi-pass flow cytometry via spectrally encoded cellular barcoding
Authors: Sheldon J. J. Kwok, Sarah Forward, Marissa D. Fahlberg, Emane Rose Assita, Sean Cosgriff, Seung Hyung Lee, Geoffrey R. Abbott, Han Zhu, Nicolas H. Minasian, A. Sean Vote, Nicola Martino, Seok-Hyun Yun
Journal: Nature Biomedical Engineering (2023)

Abstract Advances in immunology, immuno-oncology, drug discovery and vaccine development demand improvements in the capabilities of flow cytometry to allow it to measure more protein markers per cell at multiple timepoints. However, the size of panels of fluorophore markers is limited by overlaps in fluorescence-emission spectra, and flow cytometers typically perform cell measurements at one timepoint. Here we describe multi-pass high-dimensional flow cytometry, a method leveraging cellular barcoding via microparticles emitting near-infrared laser light to track and repeatedly measure each cell using more markers and fewer colours. By using live human peripheral blood mononuclear cells, we show that the method enables the time-resolved characterization of the same cells before and after stimulation, their analysis via a 10-marker panel with minimal compensation for spectral spillover and their deep immunophenotyping via a 32-marker panel, where the same cells are analysed in 3 back-to-back cycles with 10–13 markers per cycle, reducing overall spillover and simplifying marker-panel design. Cellular barcoding in flow cytometry extends the utility of the technique for high-dimensional multi-pass single-cell analyses.
Ultrafast longitudinal imaging of haemodynamics via single-shot volumetric photoacoustic tomography with a single-element detector
Authors: Yide Zhang, Peng Hu, Lei Li, Rui Cao, Anjul Khadria, Konstantin Maslov, Xin Tong, Yushun Zeng, Laiming Jiang, Qifa Zhou, Lihong V. Wang
Journal: Nature Biomedical Engineering (2023)
Modular chimeric cytokine receptors with leucine zippers enhance the antitumour activity of CAR T cells via JAK/STAT signalling
Authors: Matthew Bell, Shannon Lange, Besian I. Sejdiu, Jorge Ibanez, Hao Shi, Xiang Sun, Xiaoxi Meng, Phuong Nguyen, Morgan Sutton, Jessica Wagner, Anil KC, Deanna Langfitt, Sagar L. Patil, Haiyan Tan, Ram Vinay Pandey, Yuxin Li, Zuo-Fei Yuan, Alejandro Allo Anido, Mitchell Ho, Heather Sheppard, Peter Vogel, Jiyang Yu, Junmin Peng, Hongbo Chi, M. Madan Babu, Giedre Krenciute, Stephen Gottschalk
Journal: Nature Biomedical Engineering (2023)
Psychological inoculation strategies to fight climate disinformation across 12 countries
Authors: Tobia Spampatti, Ulf J. J. Hahnel, Evelina Trutnevyte, Tobias Brosch
Journal: Nature Human Behaviour (2023)

Decades after the scientific debate about the anthropogenic causes of climate change was settled, climate disinformation still challenges the scientific evidence in public discourse. Here we present a comprehensive theoretical framework of (anti)science belief formation and updating to account for the psychological factors that influence the acceptance or rejection of scientific messages. We experimentally investigated, across 12 countries (N = 6,816), the effectiveness of six inoculation strategies targeting these factors-scientific consensus, trust in scientists, transparent communication, moralization of climate action, accuracy and positive emotions-to fight real-world disinformation about climate science and mitigation actions. While exposure to disinformation had strong detrimental effects on participants' climate change beliefs (δ = -0.16), affect towards climate mitigation action (δ = -0.33), ability to detect disinformation (δ = -0.14) and pro-environmental behaviour (δ = -0.24), we found almost no evidence for protective effects of the inoculations (all δ < 0.20). We discuss the implications of these findings and propose ways forward to fight climate disinformation.
Deciphering Mechanisms of Respiratory Fetal-to-Neonatal Transition in Very Preterm Infants
Authors: Vincent D. Gaertner, Vanessa L. Büchler, Andreas Waldmann, Dirk Bassler, Christoph M. Rüegger
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

The respiratory mechanisms of a successful transition of preterm infants after birth are largely unknown.
Parental Income Level and Risk of Developing Type 2 Diabetes in Youth
Authors: Fu-Shun Yen, James Cheng Chung Wei, Jia-Sin Liu, Chii-Min Hwu, Chih-Cheng Hsu
Journal: JAMA Network Open (2023)

In recent years, the global incidence of type 2 diabetes in young people has increased, especially among minoritized, Indigenous, or financially disadvantaged populations. However, few studies have examined whether poverty is associated with increased risk of youth-onset type 2 diabetes.To examine the association of family income level with the risk of youth-onset type 2 diabetes.This nationwide, population-based retrospective cohort study used data from the 2008 National Health Insurance Research Database of Taiwan, with follow-up through December 31, 2019. Participants included children and adolescents aged 0 to 19 years. Data analysis was performed from June 9, 2022, to January 16, 2023.Family income, classified as very low, low, middle, and high.Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the risks of youth-onset type 2 diabetes and all-cause mortality for all income groups vs the high-income group.The cohort included a total of 5 182 893 children and adolescents (mean [SD] age, 11.2 [5.2] years; 2 477 807 girls [48.3%]). The mean (SD) follow-up duration was 9.0 (0.3) years. The incidence rates of youth-onset type 2 diabetes were 0.52 cases per 1000 person-years for the very-low-income group, 0.40 cases per 1000 person-years for the low-income group, 0.35 cases per 1000 person-years for the middle-income group, and 0.28 cases per 1000 person-years for the high-income group. Children and adolescents from very-low-income (aHR, 1.55; 95% CI, 1.41-1.71), low-income (aHR, 1.34; 95% CI, 1.27-1.41), and middle-income (aHR, 1.27; 95% CI, 1.20-1.34) families had a significantly higher hazard of youth-onset type 2 diabetes than those from high-income families. Children and adolescents from very-low-income (aHR, 2.18; 95% CI, 1.97-2.41), low-income (aHR, 1.51; 95% CI, 1.42-1.60), and middle-income (aHR, 1.22; 95% CI, 1.14-1.31) families also had a significantly higher hazard of all-cause mortality than those from high-income families. Children and adolescents who were older, female, and obese and had dyslipidemia, gout, or psychiatric disorders had a significantly higher risk of youth-onset type 2 diabetes than children without those characteristics.This population-based cohort study showed that children and adolescents from very-low-income to middle-income families had a higher hazard of youth-onset type 2 diabetes and mortality than those from high-income families. Further research to reveal the factors underlying this association may improve the accuracy of identifying individuals at greatest risk for developing type 2 diabetes in youth.
Metal–Organic Framework Based Nanozyme System for NLRP3 Inflammasome‐Mediated Neuroinflammatory Regulation in Parkinson's Disease
Authors: Qing Li, Xin Ding, Zhaohui Chang, Xiaowan Fan, Jiangpeng Pan, Ying Yang, Xin Li, Wei Jiang, Kelong Fan
Journal: Advanced Healthcare Materials (2023)

Abstract Neuroinflammation is associated with a series of pathological symptoms in Parkinson's disease (PD), including α‐synuclein aggregation and dopaminergic neuronal death. The NOD‐like receptor protein 3 (NLRP3) inflammasome plays a crucial role in neuroinflammation at the lesion site and is a promising target for PD treatment. In this study, a nanoscale metal‐organic framework (Zr‐FeP MOF) based nanozyme is fabricated using Fe‐5,10,15,20‐tetra (4‐carboxyphenyl) porphyrin (Fe‐TCPP) and Zr 6 cluster as ligands. The Zr‐FeP MOF is subsequently encapsulated with mannitol (Man)‐liposome, resulting in the formation of Zr‐FeP MOF@Man liposome (MOF@Man Liposome) nanozyme system. The in vitro studies show that this nanozyme system is effective in relieving the formation of NLRP3 inflammasome and mitochondrial dysfunction. In mouse models of PD, the nanozyme system demonstrates a significant blood–brain barrier‐crossing capability attributed to the Man‐mediated brain targeting. Additionally, transcriptomic and biochemical studies show that the nanozyme system effectively inhibits the formation and assembly of inflammasome components, mitigating the activation of glial cells and neuroinflammatory response, and ultimately regulating the pathological symptoms of PD effectively.
Skin-to-Skin Contact at Birth for Very Preterm Infants and Mother-Infant Interaction Quality at 4 Months
Authors: Siri Lilliesköld, Karoline Lode-Kolz, Siren Rettedal, Johanna Lindstedt, Agnes Linnér, Hanne Markhus Pike, Sari Ahlqvist-Björkroth, Ulrika Ådén, Wibke Jonas
Journal: JAMA Network Open (2023)

Good-quality parent-infant interactions have protective effects on infant socio-emotional and behavioral development. These interactions are especially critical for very preterm infants at risk of vulnerabilities related to immaturity. Skin-to-skin contact (SSC) has been found to improve mother-preterm infant interaction behaviors, but few studies exist regarding its benefits when initiated immediately after birth.To determine the effect of immediate SSC at birth for very preterm infants on mother-infant interaction quality at 4 months of corrected age.This secondary analysis used data from the Immediate Parent-Infant Skin-to-Skin Study (IPISTOSS), a randomized clinical trial conducted between April 1, 2018, and June 30, 2021, at 3 neonatal units in Sweden and Norway. Participants included very preterm infants (28-33 gestational weeks of age) and their parents. Four-month follow-up was concluded in December 2021. Data analyses were performed on March 16 and September 18, 2023.Infants were allocated to standard incubator care or SSC with either parent initiated at birth and continued throughout the first 6 hours after birth.The primary outcome was mother-infant interaction quality as measured with the Parent-Child Early Relational Assessment (PCERA), based on video recordings of a 5-minute free-play situation with mother-infant dyads at 4 months of corrected age. A multilevel regression analysis was performed.This analysis included 71 infants (31 twins [44%]) and 56 mothers. Infants had a mean (SD) gestational age of 31 weeks 3 (1.3) days, and more than half were male (42 [59%]); mothers had a mean (SD) age of 32 (4.9) years. There were 37 infants allocated to standard care and 34 to SSC with either parent after birth. During the first 6 hours after birth, fathers provided more SSC than mothers, with a median (IQR) of 3.25 (2.25-4.5) and 0.75 (0-2.5) hours, respectively. A statistically significant difference in 1 of 5 PCERA subscales (subscale 3: infant positive affect, communicative and social skills) was observed, with higher-quality mother-infant interaction in the SSC group at 4 months (Cohen d = 0.67 [95% CI, 0.17 to 1.17]; P = .01). This effect remained significant when adjusting for primiparity, child sex, and observation setting.In this study of the effect of immediate parent-infant SSC after very preterm birth, SSC was beneficial for the mother-infant relationship. These findings suggest that immediate SSC should be supported in the clinical setting.ClinicalTrials.gov Identifier: NCT03521310.
Impact of the physical-chemical properties of poly(lactic acid)–poly(ethylene glycol) polymeric nanoparticles on biodistribution
Authors: Mark J. Jackman, Weimin Li, Aaron Smith, David Workman, Kevin E. Treacher, Adam Corrigan, Fadi Abdulrazzaq, Silvia Sonzini, Zahid Nazir, M. Jayne Lawrence, Najet Mahmoudi, David Cant, Jonathan Counsell, Jonathan Cairns, Doug Ferguson, Eva Lenz, Saif Baquain, Christine M. Madla, Sally van Pelt, Jennifer Moss, Alison Peter, Sanyogitta Puri, Marianne Ashford, Mariarosa Mazza
Journal: Journal of Controlled Release (2023)
An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline
Authors: Nida Qadir, Sarina Sahetya, Laveena Munshi, Charlotte Summers, Darryl Abrams, Jeremy Beitler, Giacomo Bellani, Roy G. Brower, Lisa Burry, Jen-Ting Chen, Carol Hodgson, Catherine L. Hough, Francois Lamontagne, Anica Law, Laurent Papazian, Tai Pham, Eileen Rubin, Matthew Siuba, Irene Telias, Setu Patolia, Dipayan Chaudhuri, Allan Walkey, Bram Rochwerg, Eddy Fan
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP).
CK2β Regulates Hematopoietic Stem Cell Biology and Erythropoiesis
Authors: Laura Quotti Tubi, Sara Canovas Nunes, Elisa Mandato, Marco Pizzi, Nicola Vitulo, Mirco D’Agnolo, Raffaella Colombatti, Maddalena Martella, Maria Paola Boaro, Elena Doriguzzi Breatta, Anna Fregnani, Zaira Spinello, Mitja Nabergoj, Odile Filhol, Brigitte Boldyreff, Mattia Albiero, Gian Paolo Fadini, Carmela Gurrieri, Fabrizio Vianello, Gianpietro Semenzato, Sabrina Manni, Livio Trentin, Francesco Piazza
Journal: HemaSphere (2023)

The Ser-Thr kinase CK2 plays important roles in sustaining cell survival and resistance to stress and these functions are exploited by different types of blood tumors. Yet, the physiological involvement of CK2 in normal blood cell development is poorly known. Here, we discovered that the β regulatory subunit of CK2 is critical for normal hematopoiesis in the mouse. Fetal livers of conditional CK2β knockout embryos showed increased numbers of hematopoietic stem cells associated to a higher proliferation rate compared to control animals. Both hematopoietic stem and progenitor cells (HSPCs) displayed alterations in the expression of transcription factors involved in cell quiescence, self-renewal, and lineage commitment. HSPCs lacking CK2β were functionally impaired in supporting both in vitro and in vivo hematopoiesis as demonstrated by transplantation assays. Furthermore, KO mice developed anemia due to a reduced number of mature erythroid cells. This compartment was characterized by dysplasia, proliferative defects at early precursor stage, and apoptosis at late-stage erythroblasts. Erythroid cells exhibited a marked compromise of signaling cascades downstream of the cKit and erythropoietin receptor, with a defective activation of ERK/JNK, JAK/STAT5, and PI3K/AKT pathways and perturbations of several transcriptional programs as demonstrated by RNA-Seq analysis. Moreover, we unraveled an unforeseen molecular mechanism whereby CK2 sustains GATA1 stability and transcriptional proficiency. Thus, our work demonstrates new and crucial functions of CK2 in HSPC biology and in erythropoiesis.
Fish oil-based microemulsion can efficiently deliver oral peptide blocking PD-1/PD-L1 and simultaneously induce ferroptosis for cancer immunotherapy
Authors: Xin Yang, Wanqiong Li, Shuzhen Li, Shaomeng Chen, Zheng Hu, Zhuoying He, Xueqin Zhu, Xiaoshuang Niu, Xiuman Zhou, Huihao Li, Youmei Xiao, Juan Liu, Xinghua Sui, Guanyu Chen, Yanfeng Gao
Journal: Journal of Controlled Release (2023)